Low serum albumin level deteriorates prognosis in azacitidine-treated myelodysplastic syndromes patients – results of the PALG study ‘PolAZA’

Figures & data

Table 1. Baseline patient characteristics.

Characteristics	Patients
Total (N)	315
Median age in years (range)	69 (25–89)
M/F, n (%)	192/123 (61%/39%)
WHO classification n (%)
MDS	210 (67%)
CMML	39 (12%)
AML (≥20%–30% BM blasts)	66 (21%)
Neutrophil count, ×10^9 /L, median (range)	1.0 (0.0–62.0)
Hemoglobin, g/dL, median (range)	8.6 (4.4–16.8)
Platelet count, ×10^9/L, median (range)	55 (2-783)
Monocytes, ×10^9/L, median (range)	0.3 (0.0–140.0)
BM percentage blasts, median (range)	12 (0–30)
Bone marrow cellularity, n (%)	201 (64%)
Hypocellular	15 (7%)
Normo/hypercellular	186 (92%)
IPSS risk, n (%)	277 (88%)
Intermediate-2	160 (58%)
High	117 (42%)
Cytogenetics by IPSS, n (%)	274 (87%)
Good	136 (50%)
Intermediate	45 (16%)
Poor	93 (34%)
IPSS-R risk, n (%)	269 (85%)
Intermediate	30 (11%)
High	120 (45%)
Very high	119 (44%)
Cytogenetics by IPSS-R, n (%)	276 (88%)
Very good	7 (2%)
Good	130 (47%)
Intermediate	55 (20%)
Poor	64 (23%)
Very poor	20 (7%)
Ferritin level, ng/mL, median (range)	736 (20–16 000)
Serum albumin, g/dL, median (range)	3.90 (1.20–5.20)
Serum creatinine, mg/dL, median (range)	0.96 (0.33–5.98)
Performance Status (ECOG)
0	125 (51.0%)
1	92 (37.6%)
2	27 (11.0%)
3	1 (0.4%)
HCT Comorbidity Index, n (%)	283 (90%)
0–1	121 (43%)
2–3	79 (28%)
≥4	83 (29%)
MDS Comorbidity Index, n (%)	281 (89%)
Low	116 (41%)
Intermediate	108 (38%)
High	57 (20%)
Red cell transfusion dependence, n (%)
Yes	204 (65%)
No	110 (35%)
Autoimmune diseases, n (%)
Yes	28 (9%)
No	284 (91%)
Previous treatment, n (%)
Yes	57 (18%)
No	248 (78%)
Lactate dehydrogenase, n (%)
Normal	101 (37%)
High	169 (63%)
≤0.6 × ULN	19 (7%)
>0.6 × ULN	264 (93%)
Lactate dehydrogenase × ULN, number (range)	1.17 (0.35–9.00)

WHO classification, World Health Organization classification; AML, Acute Myeloid Leukemia; MDS, Myelodysplastic Syndrome; CMML, Chronic Myelomonocytic Leukemia; BM, Bone Marrow; IPSS, International Prognostic Scoring System; NA, Not applicable; IPSS-R, International Prognostic Scoring System-Revised, ECOG, Eastern Cooperative Oncology Group; HCT-CI, Hematopoietic Cell Transplantation-specific Comorbidity Index.

Table 2. Azacitidine treatment – outcomes and infections.

Number of AZA cycles, median (range)	7 (1–69)
Overall response assessment, n (%)	280
Complete response (CR)	56 (20%)
Partial response (PR)	34 (12%)
Stable disease (SD)	137 (49%)
Progressive disease (PD)	53 (19%)
Hematological improvement assessment (including CR, PR)
Erythroid response (HI-E)	94/186 (51%)
Neutrophil response (HI-N)	68/188 (36%)
Platelet response (HI-P)	93/193 (48%)
All: CR + PR + HI	154/280 (55%)
Median cycles to response, number (range)	3 (1–17)
Doubled platelet count after the first AZA cycle, n (%)	52/244 (18%)
Grade 3/4 infections, n (%)	138/315 (43%)
Overall survival (OS) status, n (%)	304
Deceased	210 (69%)
Alive	94 (31%)
Overall survival, months, median (range)	15 (1–78)

Table 3. Univariate and multivariate analysis for response.

	Univariate analysis		Multivariate analysis
	OR (95% CI)	P value	OR (95% CI)	P value
Any response (CR, PR or HI)
Hemoglobin, g/dL	1.26 (1.09–1.46)	0.002
PB blasts present	0.03 (0.00–0.36)	0.006
Bone marrow fibrosis	0.68 (0.47–1.00)	0.048
Cytogenetics IPSS	0.73 (0.54–0.99)	0.046
IPSS	0.49 (0.30–0.79)	0.004
IPSS-R	0.45 (0.28–0.72)	0
LDH, U/L	0.99 (0.99–0.99)	0.002
MRB gut colonization	0.23 (0.08–0.66)	0.006
Red cell transfusion dependence	0.46 (0.26–0.81)	0.007
ECOG performance status	0.54 (0.4–0.72)	0.000
Erythroid improvement (HI-E)
Cytogenetics IPSS	0.61(0.43–0.86)	0.005
Cytogenetics IPSS-R	0.72 (0.56–0.96)	0.014
IPSS	0.50 (0.31–0.79)	0.003
IPSS R	0.49 (0.31–0.76)	0.002
LDH, U/L	0.99 (0.99–0.99)	0.002	0.99	0.019
Neutrophil improvement (HI-N)
Lymphocytes, ×10^9/L	0.73 (0.55–0.97)	0.03	0.87	0.007
Neutrophils, ×10^9/L	0.87 (0.77–1.00)	0.046
Bone marrow fibrosis	0.54 (0.33–0.88)	0.013
Bone marrow cellularity	4.31 (1.05–17.6)	0.042
Cytogenetics IPSS	0.69 (0.48–0.99)	0.043
LDH, U/L	0.99 (0.99–1.00)	0.007
Ferritin level, ng/mL	0.99 (0.99–1.00)	0.043
Platelet improvement (HI-P)
Platelet count × 10^9/L	0.99 (0.98–0.01)	0.015	0.99	0.001
Cytogenetics IPSS	0.69 (0.49–0.97)	0.031	0.99	0.002
Cytogenetics IPSS-R	0.77 (0.59–1.00)	0.048
IPSS	0.61 (0.39–0.94)	0.027
IPSS-R	0.60 (0.39–0.91)	0.015
LDH, U/L	0.99 (0.99–0.00)	0.002
Ferritin level, ng/mL	0.99 (0.99–0.03)	0.034

CR, Complete Remission; PR, Partial Remission; HI, Hematologic Improvement; IPSS, International Prognostic Scoring System; IPSS-R, International Prognostic Scoring System-Revised; LDH, Lactate dehydrogenase; MRB, Multidrug-resistant bacteria; ECOG, Eastern Cooperative Oncology Group.

Figure 1. Prognostic value of total number of cycles, albumin level and occurrence of infection on overall survival.

Table 4. Prognostic factors for overall survival.

	Univariate analysis		Multivariate analysis
	HR (95% CI)	P value	HR (95% CI)	P value
Age	1.01 (1.00–1.03)	0.011
Lymphocyte count	1.06 (1.00–1.11)	0.038
Neutrophil count	1.03 (1.00–1.05)	0.032
Hemoglobin level	0.81 (0.74–0.88)	<0.001
Cytogenetics IPSS	1.64 (1.39–1.93)	<0.001
Cytogenetics IPSS-R	1.46 (1.29–1.64)	<0.001
IPSS	1.61 (1.30–2.00)	<0.001
IPSS-R	1.77 (1.44–2.17)	<0.001
LDH level	1.00 (1.00–1.00)	<0.001
Ferritin level	1.00 (1.00–1.00)	<0.001
Creatinine concentration	1.00 (1.00–1.00)	0.010
MRB gut colonization	1.94 (1.11–3.39)	0.019
RBC transfusion dependence	1.57 (1.17–2.11)	0.002
ECOG performance status	1.59 (1.35–1.87)	<0.001
At least 4 AZA cycles used	0.80 (0.71–0.88)	<0.001	0.90 (0.88–0.92)	0.0023
Allo-HSCT treatment used	0.43 (0.24–0.76)	0.003
Time to first response, days	0.90 (0.83–0.97)	0.008
Overall response (any response)	0.40 (0.28–0.55)	<0.01
HI-E	0.32 (0.22–0.46)	<0.01
HI-N	0.47 (0.32–0.69)	<0.001
HI-P	0.34 (0.23–0.49)	<0.001
Grade 3/4 infection	1.98 (1.49–2.63)	<0.001	1.82 (1.35–2.45)	<0.000
Albumin, g/dL	0.72 (0.56–0.91)	0.007	0.67 (0.52–0.87)	0.001

IPSS, International Prognostic Scoring System; IPSS-R, International Prognostic Scoring System-Revised; LDH, Lactate dehydrogenase; MRB, Multidrug-resistant bacteria; RBC, Red Blood Cell; ECOG, Eastern Cooperative Oncology Group; HSCT, Hematopoietic Stem Cell Transplantation; HI, Hematologic Improvement.